ArticleProceedings of the National Academy of Sciences of the United States of America2007
Mutations in the connection domain of HIV-1 reverse transcriptase increase 3'-azido-3'-deoxythymidine resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 134 citations in OpenAlex.
- Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.PloS one · 2012Trial
- Reverse Transcriptase Connection and RNase H Domain Variation in HIV-1 Subtype C Among Individuals with Virologic Failure in Botswana.Biomedicines · 2026Article
- Potent dual block to HIV-1 infection using lentiviral vectors expressing fusion inhibitor peptide mC46- and Vif-resistant APOBEC3G.Molecular therapy. Nucleic acids · 2023Article
- New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?FEMS microbiology reviews · 2023Review
- Large Multidomain Protein NMR: HIV-1 Reverse Transcriptase Precursor in Solution.International journal of molecular sciences · 2020Review
- Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase.Antimicrobial agents and chemotherapy · 2020Article
- Development of Lentiviral Vectors for HIV-1 Gene Therapy with Vif-Resistant APOBEC3G.Molecular therapy. Nucleic acids · 2019Article
- Article
- Dynamics and regulation of nuclear import and nuclear movements of HIV-1 complexes.PLoS pathogens · 2017Article
- Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil.AIDS research and human retroviruses · 2017Article
- Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.Nucleic acids research · 2016Article
- A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs.The Journal of antimicrobial chemotherapy · 2015Article
- AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase.Retrovirology · 2015Article
- Drug resistance in non-B subtype HIV-1: impact of HIV-1 reverse transcriptase inhibitors.Viruses · 2014Review
- Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors.Journal of virology · 2014Article
- The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.Journal of virology · 2014Article
- Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: from treatment to prevention.Retrovirology · 2013Review
- Examining the role of the HIV-1 reverse transcriptase p51 subunit in positioning and hydrolysis of RNA/DNA hybrids.The Journal of biological chemistry · 2013Article
- Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance.Virology · 2013Article
12 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
We previously proposed that a balance between nucleotide excision and template RNA degradation plays an important role in nucleoside reverse transcriptase inhibitor (NRTI) resistance. To explore the predictions of this concept, we analyzed the role of patient-derived C-terminal domains of HIV-1 reverse transcriptase (RT) in NRTI resistance. We found that when the polymerase domain contained previously described thymidine analog resistance mutations, mutations in the connection domain increased resistance to 3'-azido-3'-deoxythymidine (AZT) from 11-fold to as much as 536-fold over wild-type RT. Mutational analysis showed that amino acid substitutions E312Q, G335C/D, N348I, A360I/V, V365I, and A376S were associated strongly with the observed increase in AZT resistance; several of these mutations also decreased RT template switching, suggesting that they alter the predicted balance between nucleotide excision and template RNA degradation. These results indicate that mutations in the C-terminal domain of RT significantly enhance clinical NRTI resistance and should be considered in genotypic and phenotypic drug resistance studies.
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